Taxanes are diterpene compounds which have utility in the pharmaceutical field. Paclitaxel (TAXOL) is an example of a taxane which has been found to be an effective anticancer agent. The structure of paclitaxel is: ##STR1## wherein Ph is phenyl, Ac is acetyl, and Bz in benzoyl. In 1993, TAXOL was approved by the U.S. Food and Drug Administration for use in the U.S. for treatment of breast and ovarian cancers. Pharmacologically active taxanes such as paclitaxel and analogs thereof have also shown unusual efficacy for treating certain skin, lung, colon, and head and neck cancers as well as melanoma and leukemia.
There remains a problem, however, associated with paclitaxel's development and widespread use as an anticancer agent. Paclitaxel's natural source, the Pacific yew tree, is a slow growing tree native to the Pacific northwest. The scarcity of paclitaxel and the ecological impact of harvesting it have made its semi-synthesis from 10-deacetyl baccatin an attractive alternative. 10-Deacetyl baccatin is available from a more prevalent, renewable source, the needles of several taxus species.
The main challenge to developing this alternative source is the synthesis of the C-13 sidechain of the ultimate product in optically pure form and then attaching it to 10-deacetyl baccatin. Although there are chemical and enzymatic approaches reported in the literature for the production of the side chain in optically pure form, more efficient methods are still needed for more cost effective production of paclitaxel and its analogs. See J. T. Sommerfield and F. G. Wilhem, Pharmaceutical Engineering, #3, 12 (1997) and U.S. Pat. No. 5,602,272 to Li et al.